The invention relates to polynucleotide agents targeting the complement component C5 gene, and methods of using such polynucleotide agents to inhibit expression of C5 and to treat subjects having a complement component C5-associated disease, e.g., paroxysmal nocturnal hemoglobinuria.

In one aspect, the invention relates to a method of loading exosomes with oligonucleotide cargo, by incubating an oligonucleotide comprising one or more hydrophobic modifications with a population of exosomes for a period of time sufficient to allow loading of the exosomes with the oligonucleotide. Exosomes loaded with hydrophobic ally modified oligonucleotide cargo, and uses thereof, are also provided.

The present invention provides a patient positioning device, which enables the latest advances in Stereotactic Radiation Therapy. The geometry, which incorporates at least one window or lateral cut-out, is designed to allow clear treatment access to the patient during non-coplanar treatment regimes through the use of windows or lateral cut-outs. A laterally positionable diaphragm compression device allows the full use of the geometry. The development of a stand-alone device and a couch top insert device allows for a maximum number of protocol methods while minimizing the skin surface radiation dose to the patient.

A system comprises an injection well for accessing a reservoir containing a native fluid comprising a hydrocarbon. The reservoir is located below one or more caprocks, is at a first temperature, and is accessible without using large-scale hydrofracturing. The system further includes a production well in fluid communication with the reservoir, a supply apparatus configured to feed a non-water based working fluid at a second temperature that is lower than the first temperature through the injection well to the reservoir. The working fluid mixes with the native fluid to form a production fluid comprising at least a portion of the working fluid and at least a portion of the hydrocarbon at a third temperature that is higher than the second temperature. An energy recovery apparatus in fluid communication with the productions well converts energy contained in the production fluid to electricity, heat, or combinations thereof.

PRO-LEVEL tributes to Oasis, Queen and the Foo Fighters are to headline at a festival celebrating fakes in Southampton this weekend.

PEUGEOT calls its brand philosophy “unboring the future”.

When Anders Kelto listened to sports podcasts, what he usually heard was a couple of guys sitting around bantering with each other. “There was no good audio sports journalism in the world, at least that I had been exposed to,” he says. Anders is changing that. Today, the Traverse City native is out with his own podcast — it’s a sports documentary series.

Arrernte man Scott Rathman wants to see more Aboriginal artists teaching in schools to hopefully stamp out racism and stereotypical beliefs.

(United States Second Circuit) - Held that a former qui tam relator was not entitled to share in the government's recovery against a company under the False Claims Act in light of his prior voluntary dismissal of his qui tam action.

Does having a woman in charge of a country impact how that country is dealing with the pandemic?   In the midst of the Covid-19 crisis, more than one commentator has noticed that it does.  From Forbes to The Atlantic in the U.S., to think tanks around the world, “feminist leadership matters.” Forbes Magazine wrote just … Continue reading Might the Pandemic (Finally) Change the Leadership Stereotype? →

PSA Peugeot Citroën and IBM today announced a partnership to help various industries within the Internet of Things economy to analyze data to deliver new services from connected vehicles.

The team at NSKN names (now Board and Dice) sent me a review copy of Teotihuacan and I’ve had the opportunity to play several times in the months since, across all player counts, including solo against the Teotibot.

Scholars tell us that Teotihuacan was, in its prime, the largest city in the Americas as well as the sixth largest city in the world. It’s only fitting that a prominent board game designer should make it the focal point of a compelling strategy game. Daniele Tascini is that designer, and in Teotihuacan, players take on the role of noble families working to build the great city and its Pyramid of the Sun while accruing wealth and glory.

Odysseas Stamoglou is the artist behind the illustrations and tile carvings in this game. A casual glance from a player like myself (who is not steeped in deep knowledge of Mesoamerican art but has visited the Teotihuacan ruins) observes that the illustrations are reminiscent of the decorations found on structures and items from the famed city. With a bit of research I was able to track down further information on the genesis of and inspiration for the artwork, as explained by Odysseas in a BoardGameGeek.com (BGG) thread:

“All the symbols, masks and murals you see in the game are original Teotihuacano art, with some minor adjustments. The temple icons as well as the various patterns you see are not just random decorations. For example, the red pyramid, associated with the pyramid of the Sun has the fire god as its symbol. The red patterns and decorations are symbols associated with the fire god (like triangles, pointed or romboid shapes, etc). So I went out of my way to make sure each visual element is thematic and as true to the theme as possible. The great pyramid symbol and the dice icons are invented, following the style of Teotihuacan with goggle eyes and headdress for the Pyramid and Maya signs for the dice. I used the mural of the Great Goddess as inspiration for the pyramid symbol.”

Clearly, Odysseas has put a lot of time and effort into his work here and it reinforces the game’s theme extremely well. The theme and the artwork are woven together beautifully. It might have been nice to include custom dice that feature thematic Mesoamerican etchings in place of ordinary pips, but that can drive up the retail price of the game, so it may have already been discussed and dismissed by the design team as too costly. I would also like to see obsidian incorporated into the theme somehow (perhaps in a future expansion?) as that was prominent in Teotihuacan art.

Components for the game include cardboard and wooden tokens, a large main board, 4 sets of dice, and beautifully made tiles (construction material feels and looks similar to dominos) used for building the pyramid. I really love the color palette used on the main and action boards. Player aids would be nice and such an obvious plus that it’s hard to understand why they were overlooked. The good news is that there has been a collaborative effort on BGG to create effective player aids; we downloaded the latest version from beonyourway (shown below; https://boardgamegeek.com/filepage/177055/yet-another-teotihuacan-player-aid) and found them to be very useful.

Getting into the gameplay, Teotihuacan is predominantly a worker placement game (with set collection aspects) that features dice deployed as workers utilizing a rondel. Players begin the game with 3 worker dice each and take turns moving a worker die they control 1-3 spaces around the main board, from one action board to another, completing the desired action(s) on the action board their worker lands on and earning any associated victory points.

Most actions also allow the player to increase the numeric value of the worker die by 1 and when the die reaches 6 in value, the worker “ascends”, allowing the player to choose from a selection of valuable bonuses (including the acquisition of a 4^th worker die) and resetting the die back to 1 in value. The actions represented on the various action boards include earning resources (cocoa, stone, wood, gold), constructing the pyramid, decorating the pyramid, building houses, worshipping to advance on temples and earn discovery tiles, and securing technology.

Extra actions or bonuses may be granted to a player when they have more than one die on an action board at the time they complete the action on that board – this is usually a result of moving a die to an action board where the player previously moved a die but some discovery tile bonuses allow players to move more than one worker die at a time, which can also lead to the accumulation of multiple dice belonging to one player on an action board. It’s not exclusively take, take, take in Teotihuacan. Players must give up resources in order to complete most actions. Additionally, they must pay resources – specifically cocoa - at the end of each phase or “eclipse” of the game (payment is proportionally to the number of worker dice they control and the numeric value of those dice) as well as whenever they wish to take an action where other players currently have worker dice positioned (payment is proportional to the number of other players who have worker dice already on that action board).

Almost every game has gone down the same for me– I find creative ways to pull out far ahead of the other players in the beginning, but I usually struggle with building an engine and eventually their engines take off and they overcome me. I couldn’t even pull off a win against the Teotibot on the easiest level. I finally had a win last week by focusing heavily on the construction action board, as three of the technologies gave bonuses for that action.

There are many ways to score points in Teotihuacan and it opens up a lot of avenues for creatively driving point accrual. The many options also allow for replay experiences that feel like a different game each time. Of course, a multitude of choices can also lead to analysis paralysis and Teotihuacan can suffer from this, dragging the playing time out typically anywhere from 90 to 120 minutes on average in our house.

Strategy tip: players need to be flexible and adapt tactics each game, taking  into consideration the action board arrangement and the available technologies on the alchemy action board.

Teotihuacan is the only game in my collection with a Mesoamerican theme, one of the few incorporating a rondel, and as an added plus, it includes solo mode.  It has so much to offer including a well-researched and implemented theme, a consistent intellectual challenge across all player counts, and quality components. All of these features suggest it would be a great addition to any game library, but it’s the ever-changing gameplay created by the variable action board placement and technologies that really compelled me to give Teotihuacan a permanent home in my game collection.

-------------------------------------------------

Publisher: NSKN Games (now Board and Dice)
Players: 1-4
Actual Playing Time (vs the guideline on the box): 90-120 minutes
Game type: Worker Placement, Rondel, Set Collection

Rating:

Jenni’s rating scale:
OUI: I would play this game again; this game is ok. I probably would not buy this game myself but I would play it with those who own it and if someone gave it to me I would keep it.
OUI OUI: I would play this game again; this game is good. I would buy this game.
OUI OUI OUI: I LOVE THIS GAME. I MUST HAVE THIS GAME.
NON: I would not play this game again. I would return this game or give it away if it was given to me

Costume designer Arianne Phillips and Quentin Tarantino had a no tie-dye mindset going into the late-'60s-set film 'Once Upon a Time... in Hollywood.'

Are you a geotechnical engineering graduate student, or recent graduate, with a passion for solving soil work and foundation problems? Do you enjoy being outdoors and getting your hands dirty, both figuratively and literally? Are you interested in being part of a team of creative, innovative and har

Incorporation of ribonucleotides into DNA can severely diminish genome integrity. However, how ribonucleotides instigate DNA damage is poorly understood. In DNA, they can promote replication stress and genomic instability and have been implicated in several diseases. We report here the impact of the ribonucleotide rATP and of its naturally occurring damaged analog 1,N6-ethenoadenosine (1,N6-ϵrA) on translesion synthesis (TLS), mediated by human DNA polymerase η (hpol η), and on RNase H2–mediated incision. Mass spectral analysis revealed that 1,N6-ϵrA in DNA generates extensive frameshifts during TLS, which can lead to genomic instability. Moreover, steady-state kinetic analysis of the TLS process indicated that deoxypurines (i.e. dATP and dGTP) are inserted predominantly opposite 1,N6-ϵrA. We also show that hpol η acts as a reverse transcriptase in the presence of damaged ribonucleotide 1,N6-ϵrA but has poor RNA primer extension activities. Steady-state kinetic analysis of reverse transcription and RNA primer extension showed that hpol η favors the addition of dATP and dGTP opposite 1,N6-ϵrA. We also found that RNase H2 recognizes 1,N6-ϵrA but has limited incision activity across from this lesion, which can lead to the persistence of this detrimental DNA adduct. We conclude that the damaged and unrepaired ribonucleotide 1,N6-ϵrA in DNA exhibits mutagenic potential and can also alter the reading frame in an mRNA transcript because 1,N6-ϵrA is incompletely incised by RNase H2.

Incorporation of ribonucleotides into DNA can severely diminish genome integrity. However, how ribonucleotides instigate DNA damage is poorly understood. In DNA, they can promote replication stress and genomic instability and have been implicated in several diseases. We report here the impact of the ribonucleotide rATP and of its naturally occurring damaged analog 1,N6-ethenoadenosine (1,N6-ϵrA) on translesion synthesis (TLS), mediated by human DNA polymerase η (hpol η), and on RNase H2–mediated incision. Mass spectral analysis revealed that 1,N6-ϵrA in DNA generates extensive frameshifts during TLS, which can lead to genomic instability. Moreover, steady-state kinetic analysis of the TLS process indicated that deoxypurines (i.e. dATP and dGTP) are inserted predominantly opposite 1,N6-ϵrA. We also show that hpol η acts as a reverse transcriptase in the presence of damaged ribonucleotide 1,N6-ϵrA but has poor RNA primer extension activities. Steady-state kinetic analysis of reverse transcription and RNA primer extension showed that hpol η favors the addition of dATP and dGTP opposite 1,N6-ϵrA. We also found that RNase H2 recognizes 1,N6-ϵrA but has limited incision activity across from this lesion, which can lead to the persistence of this detrimental DNA adduct. We conclude that the damaged and unrepaired ribonucleotide 1,N6-ϵrA in DNA exhibits mutagenic potential and can also alter the reading frame in an mRNA transcript because 1,N6-ϵrA is incompletely incised by RNase H2.

Purpose: The aim of this retrospective multicentric study was to develop and evaluate a prognostic FDG PET/CT radiomics signature in early-stage non-small cell lung cancer (NSCLC) patients treated with stereotactic radiotherapy (SBRT). Material and Methods: Patients from 3 different centers (n = 27, 29 and 8) were pooled to constitute the training set, whereas the patients from a fourth center (n = 23) were used as the testing set. The primary endpoint was local control (LC). The primary tumour was semi-automatically delineated in the PET images using the Fuzzy locally adaptive Bayesian algorithm, and manually in the low-dose CT images. A total of 184 IBSI-compliant radiomic features were extracted. Seven clinical and treatment parameters were included. We used ComBat to harmonize radiomic features extracted from the four institutions relying on different PET/CT scanners. In the training set, variables found significant in the univariate analysis were fed into a multivariate regression model and models were built by combining independent prognostic factors. Results: Median follow-up was 21.1 (1.7 – 63.4) and 25.5 (7.7 – 57.8) months in training and testing sets respectively. In univariate analysis, none of the clinical variables, 2 PET and 2 CT features were significantly predictive of LC. The best predictive models in the training set were obtained by combining one feature from PET, namely information correlation 2 (IC2) and one from CT (Flatness), reaching a sensitivity of 100% and a specificity of 96%. Another model combining 2 PET features (IC2 and Strength), reached sensitivity of 100% and specificity of 88%, both with an undefined hazard ratio (HR) (p<0.001). The latter model obtained an accuracy of 0.91 (sensitivity 100%, specificity 81%), with a HR undefined (P = 0.023) in the testing set, however other models relying on CT radiomics features only or the combination of PET and CT features failed to validate in the testing set. Conclusion: We showed that two radiomic features derived from FDG PET were independently associated with LC in patients with NSCLC undergoing SBRT and could be combined in an accurate predictive model. This model could provide local relapse-related information and could be helpful in clinical decision-making.

Mass spectrometry (MS) and proteomics offer comprehensive characterization and identification of microorganisms and discovery of protein biomarkers that are applicable for diagnostics of infectious diseases. The use of biomarkers for diagnostics is widely applied in the clinic and the use of peptide biomarkers is increasingly being investigated for applications in the clinical laboratory. Respiratory-tract infections are a predominant cause for medical treatment, although, clinical assessments and standard clinical laboratory protocols are time-consuming and often inadequate for reliable diagnoses. Novel methods, preferably applied directly to clinical samples, excluding cultivation steps, are needed to improve diagnostics of infectious diseases, provide adequate treatment and reduce the use of antibiotics and associated development of antibiotic resistance. This study applied nano-liquid chromatography (LC) coupled with tandem MS, with a bioinformatics pipeline and an in-house database of curated high-quality reference genome sequences to identify species-unique peptides as potential biomarkers for four bacterial pathogens commonly found in respiratory tract infections (RTIs): Staphylococcus aureus; Moraxella catarrhalis; Haemophilus influenzae and Streptococcus pneumoniae. The species-unique peptides were initially identified in pure cultures of bacterial reference strains, reflecting the genomic variation in the four species and, furthermore, in clinical respiratory tract samples, without prior cultivation, elucidating proteins expressed in clinical conditions of infection. For each of the four bacterial pathogens, the peptide biomarker candidates most predominantly found in clinical samples, are presented. Data are available via ProteomeXchange with identifier PXD014522. As proof-of-principle, the most promising species-unique peptides were applied in targeted tandem MS-analyses of clinical samples and their relevance for identifications of the pathogens, i.e. proteotyping, was validated, thus demonstrating their potential as peptide biomarker candidates for diagnostics of infectious diseases.

Incorporation of ribonucleotides into DNA can severely diminish genome integrity. However, how ribonucleotides instigate DNA damage is poorly understood. In DNA, they can promote replication stress and genomic instability and have been implicated in several diseases. We report here the impact of the ribonucleotide rATP and of its naturally occurring damaged analog 1,N6-ethenoadenosine (1,N6-ϵrA) on translesion synthesis (TLS), mediated by human DNA polymerase η (hpol η), and on RNase H2–mediated incision. Mass spectral analysis revealed that 1,N6-ϵrA in DNA generates extensive frameshifts during TLS, which can lead to genomic instability. Moreover, steady-state kinetic analysis of the TLS process indicated that deoxypurines (i.e. dATP and dGTP) are inserted predominantly opposite 1,N6-ϵrA. We also show that hpol η acts as a reverse transcriptase in the presence of damaged ribonucleotide 1,N6-ϵrA but has poor RNA primer extension activities. Steady-state kinetic analysis of reverse transcription and RNA primer extension showed that hpol η favors the addition of dATP and dGTP opposite 1,N6-ϵrA. We also found that RNase H2 recognizes 1,N6-ϵrA but has limited incision activity across from this lesion, which can lead to the persistence of this detrimental DNA adduct. We conclude that the damaged and unrepaired ribonucleotide 1,N6-ϵrA in DNA exhibits mutagenic potential and can also alter the reading frame in an mRNA transcript because 1,N6-ϵrA is incompletely incised by RNase H2.

Here's a trick question, so think carefully before you answer: If someone mentions the word "beast" to you, which word would you match it with?

Ageism -- United States.

London : H.K. Lewis, 1891.

Berlin : A. Hirschwald, 1870.

Watch the debut of "Our Stories - Natalie Chou" on Sunday, May 10 at 12:30 p.m. PT/ 1:30 p.m. MT on Pac-12 Network.

From age 17, Ana Maria prayed to serve God in Switzerland. While she waited, she became a dance instructor with no idea dance would become her ministry.

From age 17, Ana Maria prayed to serve God in Switzerland. While she waited, she became a dance instructor with no idea dance would become her ministry.

From age 17, Ana Maria prayed to serve God in Switzerland. While she waited, she became a dance instructor with no idea dance would become her ministry.

Candidate genes involved in thrombophilia, inflammation, and preterm birth have previously been associated with cerebral palsy. Most studies to date have included small cohorts, did not allow for multiple testing, and require replication.

This study of children with cerebral palsy and their mothers did not confirm previously reported candidate gene associations. Prothrombin gene mutation was associated with hemiplegia in children born at term to mothers with a reported infection during pregnancy. (Read the full article)

From age 17, Ana Maria prayed to serve God in Switzerland. While she waited, she became a dance instructor with no idea dance would become her ministry.

From age 17, Ana Maria prayed to serve God in Switzerland. While she waited, she became a dance instructor with no idea dance would become her ministry.

From age 17, Ana Maria prayed to serve God in Switzerland. While she waited, she became a dance instructor with no idea dance would become her ministry.

From age 17, Ana Maria prayed to serve God in Switzerland. While she waited, she became a dance instructor with no idea dance would become her ministry.

From age 17, Ana Maria prayed to serve God in Switzerland. While she waited, she became a dance instructor with no idea dance would become her ministry.

From age 17, Ana Maria prayed to serve God in Switzerland. While she waited, she became a dance instructor with no idea dance would become her ministry.

From age 17, Ana Maria prayed to serve God in Switzerland. While she waited, she became a dance instructor with no idea dance would become her ministry.

What we call education inequality defines how—and even if—we solve it, write three researchers.

Last week, Corvias announced that it had entered the final phase of its geothermal installation and energy upgrades effort at the U.S. Army’s Fort Polk in West-Central Louisiana, a milestone that once complete will not only modernize the aging infrastructure but save the Army significant money and benefit military families.

The U.K. could be producing electricity from a geothermal plant for the first time early next decade after drilling at a site in southwest England showed it could become a viable part of the renewable energy mix.

In late February, Hawaiian Electric Companies announced that they have achieved a consolidated 27 percent renewable portfolio standard in 2018, even with the loss of Hawaii Island’s geothermal resource for most of the year following the Kilauea volcanic eruption. Hawaii has a goal of reaching 100 percent renewable energy by 2045.

Utilities are a natural partner for the geothermal heat pump (GHP) industry. Why? Because utilities have a broad consumer base and infrastructure, and need to both build load (sales) and levelize that demand to make the most efficient use of their electrical generation capacity throughout the year.  GHPs are a technology that fills that niche.

Italy’s Five Star Movement used to rave about towns like Montieri, a village in the verdant Tuscan foothills that burns little coal or natural gas. Instead, the local power plant harnesses steam rising naturally from hot springs deep underground to generate electricity.

Italy’s government is dragging its feet on incentives for geothermal power and one local politician has decided to take his protest to the extreme.

This week the University of Nevada, Reno announced two discoveries in the Great Basin by the Nevada Bureau of Mines and Geology using a previously untried method for finding unknown, hidden geothermal resources.

Reykjavik Geothermal, a power developer backed by hedge fund billionaire Paul Tudor Jones II, is about to kick off a $4.4 billion project to bring geothermal energy to Ethiopia.